Epstein-Barr Virus (EBV) and Herpes simplex subtype 2 (HSV-2) are two DNA-containing herpes viruses which have been implicated as etiologic agents in Burkitt's lymphoma (EB3), nasopharyngeal carcinoma (EBV) and cervical carcinoma (HSV-2). I propose to determine if these viruses share properties with other known DNA-tumor viruses. In particular, I will determine whether viral DNA forms a stable association with cellular DNA from tumor cells. Viral DNA's will be purified and employed in an in vitro reaction with E. coli RNA polymerase to prepare a radiolabeled RNA complementary to viral DNA (cRNA). This cRNA will then be used as a specific probe to detect viral nucleotide sequences in tumor cell DNA by nucleic acid hybridization techniques. Equilibrium and velocity sedimentation of cellular DNA's in alkaline gradients followed by nucleic acid hybridization of gradient fractions will be carried out to determine if viral and cellular DNA's are linked by covalent bonds. Nucleic acid hybridization competition experiments will be performed to determine if different segments of the EBV genome are transcribed in virus producing and non-virus producing lines of Burkitt's lymphoma cells and in leucocytes from patients with infectious mononucleosis. Correlation of the species of EBV-specific RNA transcribed with the production of EBV early and capsid antigens will be attempted. Experiments to detect EBV nucleic acids and antigens in tissues other than those of the lymphoreticular system will be undertaken.